UCSD study shows liver disease likely to run in families

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SAN DIEGO -- Family members of children diagnosed with
non-alcoholic fatty liver disease (NAFLD) should be considered at
high risk for the disease and tested for it as part of a routine
medical examination, even if they don't show symptoms, according to
a recent study by researchers at the UC San Diego School of
Medicine.

The results were published in the May edition of the journal
Gastroenterology.

"As we suspected, NAFLD is not simply about weight, but rather
is highly familial and likely genetic," said principal investigator
Dr. Jeffrey B. Schwimmer, associate professor of pediatrics and
director of the Fatty Liver Clinic at Rady Children's Hospital-San
Diego.

Non-alcoholic fatty liver disease is now the most common cause
of chronic liver disease in the United States. NAFLD refers to a
spectrum of liver disease that begins with liver cells abnormally
storing fat, in the absence of chronic alcohol use. It can be mild
in some people, but with the progressive form (steatoehepatitis),
there is risk for cirrhosis, liver cancer, and liver-related death.
Based upon clinical observation, doctors have speculated that
non-alcoholic fatty liver disease may be a genetic disease, but
lacked scientific support for this idea.

The study takes a major step in building the case that
non-alcoholic fatty liver disease is genetic. The research team
studied 44 children with and without non-alcoholic fatty liver
disease and 152 family members of these children. To determine the
amount of fat in the liver of each participant, they used a
magnetic resonance imaging technique developed at UC San Diego. The
researchers also did tests to exclude other factors that can cause
a fatty liver other than NAFLD.

The researchers found that whether or not a given person had
non-alcoholic fatty liver disease was highly heritable -- whether
or not the child had non-alcoholic fatty liver disease was a major
determinant of the amount of liver fat present in the other family
members.

In the families of overweight children without NAFLD, siblings
and parents had non-alcoholic fatty liver disease at rates that
were similar to the background population's rates. Rates were much
higher in family members of children with non-alcoholic fatty liver
disease; it was present in 59 percent of siblings and 78 percent of
parents. In most cases, the relatives did not know that they had
the disease. In a few cases, the disease was already very advanced,
even in the absence of symptoms.

"Being overweight is a risk factor for NAFLD, but this is
strongly modified by the underlying genetics," said Schwimmer. "So
some people can have high body weights without any storage of fat
in the liver. But in susceptible families, there's an additive
effect. Regardless of weight, they are more likely to have NAFLD
for genetic reasons. In addition, the more overweight such a person
is, the more likely they are to have dangerous amounts of fat in
their liver."

The researchers recommend that if one family member tests
positive for non-alcoholic fatty liver disease, other family
members should talk to their doctors immediately. Early detection
could catch non-alcoholic fatty liver disease at a stage where the
disease is reversible and further complications may be prevented
before cirrhosis sets in.

Schwimmer hopes that further studies will disclose specific
genetic and environmental factors that influence the development
and severity of the disease, which could provide helpful
information to doctors.

"Understanding that this disease runs in families may help an
entire family create a healthy lifestyle with regular exercise and
a heart-healthy/liver-healthy diet," said Schwimmer.

Previous studies by UC San Diego investigators showed that:

- Non-alcoholic fatty liver disease is present in 9.6 percent of
the children and adolescents living in San Diego County;

- Nearly all children with non-alcoholic fatty liver disease are
insulin resistant;

- In children, non-alcoholic fatty liver disease is a major risk
factor for diabetes and cardiovascular disease.